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PON1 comprises a potential candidate for\n                      <jats:italic>in vivo<\/jats:italic>\n                      therapeutics, as an anti-atherogenic agent, and for detoxification of pesticides and nerve agents. Because human PON1 exhibits limited stability, engineered, recombinant PON1 (rePON1) variants that were designed for higher reactivity, solubility, stability, and bacterial expression, are candidates for treatment. This work addresses the feasibility of\n                      <jats:italic>in vivo<\/jats:italic>\n                      administration of rePON1, and its HDL complex, as a potentially therapeutic agent dubbed BL-3050.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      For stability studies we applied different challenges related to the\n                      <jats:italic>in vivo<\/jats:italic>\n                      disfunctionalization of HDL and PON1 and tested for inactivation of PON1's activity. We applied acute, repetitive administrations of BL-3050 in mice to assess its toxicity and adverse immune responses. The\n                      <jats:italic>in vivo<\/jats:italic>\n                      efficacy of recombinant PON1 and BL-3050 were tested with an animal model of chlorpyrifos-oxon poisoning.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Inactivation studies show significantly improved\n                      <jats:italic>in vitro<\/jats:italic>\n                      lifespan of the engineered rePON1 relative to human PON1. Significant sequence changes relative to human PON1 might hamper the\n                      <jats:italic>in vivo<\/jats:italic>\n                      applicability of BL-3050 due to adverse immune responses. However, we observed no toxic effects in mice subjected to repetitive administration of BL-3050, suggesting that BL-3050 could be safely used. To further evaluate the activity of BL-3050\n                      <jats:italic>in vivo<\/jats:italic>\n                      , we applied an animal model that mimics human organophosphate poisoning. In these studies, a significant advantages of rePON1 and BL-3050 (&gt;87.5% survival versus &lt;37.5% in the control groups) was observed. Furthermore, BL-3050 and rePON1 were superior to the conventional treatment of atropine-2-PAM as a prophylactic treatment for OP poisoning.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      <jats:italic>In vitro<\/jats:italic>\n                      and\n                      <jats:italic>in vivo<\/jats:italic>\n                      data described here demonstrate the potential advantages of rePON1 and BL-3050 for treatment of OP toxicity and chronic cardiovascular diseases like atherosclerosis. The\n                      <jats:italic>in vivo<\/jats:italic>\n                      data also suggest that rePON1 and BL-3050 are stable and safe, and could be used for acute, and possibly repeated treatments, with no adverse effects.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/1472-6904-9-18","type":"journal-article","created":{"date-parts":[[2009,11,17]],"date-time":"2009-11-17T14:14:57Z","timestamp":1258467297000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["In vivo administration of BL-3050: highly stable engineered PON1-HDL complexes"],"prefix":"10.1186","volume":"9","author":[{"given":"Leonid","family":"Gaidukov","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dganit","family":"Bar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiri","family":"Yacobson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esmira","family":"Naftali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Kaufman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rinat","family":"Tabakman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan S","family":"Tawfik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Etgar","family":"Levy-Nissenbaum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2009,11,17]]},"reference":[{"issue":"16","key":"80_CR1","doi-asserted-by":"publisher","first-page":"6371","DOI":"10.1021\/bi047440d","volume":"44","author":"O Khersonsky","year":"2005","unstructured":"Khersonsky O, Tawfik DS: Structure-Reactivity Studies of Serum Paraoxonase PON1 Suggest that Its Native Activity Is Lactonase. 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